Arachidonate 12S-lipoxygenase of platelet-type in hepatic stellate cells of methionine and choline-deficient diet-fed mice
Arachidonate 12S-lipoxygenase of platelet-type in hepatic stellate cells of methionine and choline-deficient diet-fed mice
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DOI：
10.1093/jb/mvaa062
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发表时间：
2020-11-01
影响因子：
2.7
通讯作者：
Takahashi, Yoshitaka
中科院分区：
文献类型：
--
作者：
Mori, Yoshiko;Kawakami, Yuki;Takahashi, Yoshitaka
12-脂氧合酶在非酒精性脂肪性肝炎（NASH）进展中的作用被提出，尽管其潜在机制尚不完全清楚。12s -脂氧合酶的催化活性在正常小鼠的肝细胞质中几乎没有观察到，但在饲喂蛋氨酸和胆碱缺乏（MCD）饮食的NASH模型小鼠中却可以明显检测到。产物谱、底物特异性和免疫原性表明该酶为血小板型同种异构体。MCD日粮喂养小鼠肝脏血小板型12s -脂氧合酶mRNA和蛋白的表达水平显著高于正常鼠。免疫组化分析显示，血小板型12s -脂氧合酶与1-平滑肌肌动蛋白和维生素A在沿肝窦分布的细胞中共定位。上述结果表明，MCD饮食喂养小鼠肝星状细胞活化过程中血小板型12s -脂氧合酶表达水平升高，提示该酶可能参与肝纤维化的病理生理过程。
A role of 12-lipoxygenase in the progression of non-alcoholic steatohepatitis (NASH) is suggested, although the underlying mechanism is not entirely understood. The catalytic activity of 12S-lipoxygenase that was hardly observed in liver cytosol of normal chow-fed mice was clearly detectable in that of NASH model mice prepared by feeding a methionine and choline-deficient (MCD) diet. The product profile, substrate specificity and immunogenicity indicated that the enzyme was the platelet-type isoform. The expression levels of mRNA and protein of platelet-type 12S-lipoxygenase in the liver of MCD diet-fed mice were significantly increased compared with those of normal chow-fed mice. Immunohistochemical analysis showed that platelet-type 12S-lipoxygenase colocalized with 1-smooth muscle actin as well as vitamin A in the cells distributing along liver sinusoids. These results indicate that the expression level of platelet-type 12S-lipoxygenase in hepatic stellate cells was increased during the cell activation in MCD diet-fed mice, suggesting a possible role of the enzyme in pathophysiology of liver fibrosis.